The present invention relates to the use of Interferon-xcex1 subtypes, particularly IFN-xcex18, and/or IFN-xcex11, as adjuvants for vaccines. In addition, it relates to the use of these Interferon subtypes to stimulate proliferation of B lymphocytes.
Type I interferons (IFN) are a family of closely related glycoproteins containing many IFN-xcex1 subtypes and one IFN-xcex2 subspecies. At least 23 different human IFN-xcex1 subtypes have been identified by analysis of human cDNA libraries and by protein analysis of the IFNs produced by stimulated lymphoblastoid cells. The reasons for this heterogeneity are not yet known. Previous studies have suggested that all Type I IFNs bind to an identical receptor and therefore have identical effects. However a mutant cell line that responds only to IFN-xcex2 but not IFN-xcex1 has been identified showing that these two IFN subspecies bind to a different receptor and may therefore have different effects. Studies on the transmembrane human IFN receptor have shown that if this receptor is transfected into murine cells the cells respond only to some IFN subtypes, showing that a second receptor component is required to allow cells to respond to IFN and that the murine equivalent of this component is able to distinguish between different IFN subtypes. Molecular analysis of the human Type I IFN receptor thus suggests that the receptor may be able to distinguish between different IFN subtypes.
A number of studies have compared the effects of different IFN-xcex1 subtypes on the antiviral activities of human cell lines. Zoon et al (J. Biol. Chem. 267: 15210-16 (1992) studied IFNs that were obtained from HPLC purification of natural IFN and found no gross differences in their antiviral activities. However, Sperber et al, J. Interferon. Res. 12 363-368 (1992) examined the effects of different recombinant IFN-xcex1 subtypes on cells infected with the human immunodeficiency virus (HIV) and found marked differences in their antiviral properties. W)95/24212 disclosed that different IFN-xcex1 subtypes were effective antiviral agents in different cell types. Thus, it is possible to target viral infections in say the liver by the use of particular subtypes, eg IFN-xcex18.
B cells or B lymphocytes are a subset of lymphocytes found in secondary lymphoid organs as well as circulating in the blood. They are characterised by the possession of antigen-specific cell surfaceimmunoglobulin molecules of a single antigen-binding specificity which act as receptors for antigen. The interaction of antigen with the cell-surface immunoglobulin is in part responsible for subsequent proliferation of the B cells and their development into antibody-secreting plasma cells.
We have now found that B cell proliferation can be induced by certain IFN-xcex1 subtypes. Thus, it is possible to stimulate a subject""s immune response and in particular the subtypes can be used as adjuvants to increase the effectiveness of vaccines.
Thus, in a first aspect the present invention provides an adjuvant for a vaccine comprising an IFN-xcex1 subtype. In particular the invention provides an adjuvant for a vaccine which comprises IFN-xcex18 and/or IFN-xcex114.
The adjuvant of the present invention can be co-administered with a vaccine or could itself form part of the vaccine itself. Thus, in a second aspect the present invention provides a vaccine comprising at least one IFN-xcex1 subtype, preferably IFN-xcex18 and/or IFN-xcex114.
The skilled person will appreciate that the particular antigen or antigens which the vaccine comprises is/are not important. Due to the ability of particular IFN-xcex1 subtypes to stimulate B cell proliferation they find general use as adjuvants and enable enhanced immune responses to be obtained upon vaccination.
In a third aspect the present invention provides a method of vaccinating a subject which comprises the step of co-administering to the subject an IFN-xcex1 subtype. As already discussed herein, the co-administration can be separate or the IFN-xcex1 subtype can be administered as part of the vaccine itself.
In a final aspect the present invention provides a method for stimulating proliferation of B cells which comprises the step of bringing one or more B cells into contact with at least one IFN-xcex1 subtype, preferably IFN-xcex18 and/or IFN-xcex114.
The invention will now be described by means of the following example which should not be construed as in any way limiting the invention.
The example refers to the FIGURE which shows proliferation of tonsillar B cells in response to anti-IgM and IFN-xcex1 subtypes.